A phase I, multi-center, open-label, drug-drug interaction study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on TKI258 (dovitinib) pharmacokinetics in patients with advanced solid tumors.
- Conditions
- advanced cancersolid tumors10027655
- Registration Number
- NL-OMON39285
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 12
1. Patients diagnosed with either an advanced solid tumor, excluding breast cancer, or advanced hepatocellular carcinoma, which has progressed despite standard therapy, or for which no standard therapy exists
2. ECOG performance status <= 2
3. Absolute neutrophil count >= 1.5 x 109/L
4. Platelets >= 100 x 109/L
5. Hemoglobin >= 8.0 g/dL = 4.96 mmol/L
6. Serum creatinine <= 1.5 x ULN or 24-hour urine collection creatinine clearance >= 30 mL/min/1.73m2 (>= 50 mL/min/1.73m2 in the presence of proteinuria as defined in inclusion criterion #9) or,
Serum creatinine > 1.5 - 3 x ULN with calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
7. Serum total bilirubin <= 1.5 x ULN
8. AST and ALT <= 3.0 x ULN
9. Urine dipstick negative for proteinuria or, if documentation of +1 results (+ 2 for patients with RCC) for protein on dipstick reading, then total urinary protein <= 500 mg and measured creatinine clearance >= 50 L/min/1.73m3 from a 24 hour urine collection
10. Patients with a life expectance of > 3 month
1. Patients with brain metastases as assessed by mandatory radiologic imaging at screening
2. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
3. Prior anticancer therapies:
•targeted small molecule therapy <= 2 weeks prior to starting study drug,
•monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy <= 4 weeks prior to starting study drug,
•nitrosourea or mitomycin-C <= 6 weeks prior to starting study drug
•radiotherapy <= 4 weeks prior to starting the study drug (palliative radiotherapy for bone lesions <= 2 weeks prior to starting study drug is allowed)
and not recovered from anti-cancer therapy related toxicities
4. Major surgery <= 4 weeks prior to starting study treatment, or who have not recovered from side effects of such therapy
5. Pulmonary embolism or untreated deep venous thrombosis within 6 months prior to starting study drug
6. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
•History or presence of serious uncontrolled ventricular arrhythmias
•Clinically significant resting bradycardia
•LVEF < 50% (ECHO)or < 45% (MUGA)
•Myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack within 6 months prior to starting study drug
•Uncontrolled hypertension defined by a SBP >= 160 mm Hg and/or DBP >= 100 mm Hg, with or without anti-hypertensive medication(s). Initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry
7. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib.
8. Cirrhosis, chronic active hepatitis, or chronic persistent hepatitis.
9. Current use of prasugrel, clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. Treatment with low doses of warfarin (e.g., <= 2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) is allowed.
10. Other concurrent severe and/or uncontrolled concomitant medical conditions
11. Use of potent and moderate CYP1A2 inhibitors or potent and moderate CYP3A inhibitors within 5 days prior to starting study treatment, or during the PK phase (i.e., days 1-28, inclusive, of the PK phase).
12. CYP1A2 inducers (including tobacco) or CYP3A inducers within 30 days prior to starting study treatment, or during the PK phase (i.e., days 1-28, inclusive, of the PK phase))
13. Actively taking antidepressants, benzodiazepines, serotonergic drugs, and/or monoamine oxidase inhibitors (MAOIs).
14. Expected alcohol intake to exceed 1 drink/day within 3 days prior to the days of blood sample collection for PK assessment in the PK phase (i.e., <= 3 days prior to days 19 and 26 of the PK phase) and throughout the timeframe they are taking fluvoxamine (i.e., days 26, 27 and 28 of the PK phase).
15. Grapefruits, pomegranates, star fruits, Seville oranges or products containing the juice of each within 3 days prior to the days of blood sample collection for PK assessment in the PK phase (i.e., <= 3 days prior to days 19 and 26 of the PK phase).
16. Homeopathic or naturopathic medicines within 5 days prior to the days of blood sample collection for PK assessment in the PK phase (i.e., <= 5 days prior to days 19 and
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>TKI258 (dovitinib) Pharmacokinetic parameters:<br /><br>Primary - AUC 0-72h, Cmax; and secondary - T1/2, Cmin,ss, Tmax, AUC 0-24h</p><br>
- Secondary Outcome Measures
Name Time Method <p>Incidence and severity of adverse events according to the CTCAE criteria<br /><br>Version 4.03, unless otherwise specified; changes from baseline in clinical<br /><br>laboratory tests, physical examinations, vital signs, ECGs, and cardiac imaging<br /><br>Overall response based on investigator assessment and best overall response<br /><br>using RECIST version 1.1</p><br>